Interactions of the plasma membrane and extracellular materials are critically important events during functional development of lungs. Neither the nature of these interactions nor their cellular functions are presently understood. Our objectives are to determine the nature, mechanisms, and function of membrane-matrix interactions in the normal and diseased lung cells. We will test the hypothesis that interactions between cells and extracellular molecules can be mediated by multiple mechanisms, even within the same cell. An important goal will be unambiguous identification of fibroblast and epithelial cell receptors for fibronectin, laminin, and collagens. We have raised monoclonal antibodies to isolated membranes containing membrane-matrix linkage complexes for identification of membrane receptors. These monoclonal antibodies will be used to probe binding interactions and protein localization of membrane and matrix components that allows a direct examination of mechanisms of such interactions. Function-oriented studies using laminin- or fibronectin-coupled substrata will be performed to determine specific binding interactions of lung cells to these linker glycoproteins and between purified 140 Kd membrane proteins and fibronectin, and to examine the possibility that degradation of these components may be a potential mechanism for alteration of such interactions Ultrathin frozen section immunoelectron microscopy will resolve absolute and relative depositions of molecules in cultured lung cells and in alveolar walls during functional development of lungs and in pulmonary diseases. The information obtained may provide clues about mechanisms and control of cell-matrix interactions and suggest methods for the successful diagnosis and treatment of pulmonary patients.